The present invention relates to a novel medicament capsule for rectal application. More particularly, the invention relates to a medicament form of a hard capsule containing a therapeutically effective ingredient capable of being absorbed through the rectum, of which the releasability of the effective ingredient is markedly improved.
As is well known, a variety of medicines are used in a medicament form suitable for rectal application with an object either to obtain a systemic action or to obtain a local action of the effective ingredient. Several of the examples of the medicines of which a systemic action is desired by the rectal application include antipyretic, anodynic and antiphlogistic agents such as aspirin, aminopyrin, sulpyrin, phenylbutazone, oxyphenbutazone, indomethacin and the like, antispasmodic agents such as butylscopolamine bromide and the like, antibiotics such as erythromycin and the like, antituberculosis agents such as ethionamide and the like, and others. Those medicines of which a local action is desired include, on the other hand, astringents, local anesthetics and bactericidal agents with or without admixture of an adrenocortical hormone for haemorrhoids.
At any rate, the effective ingredient in the medicine administrated by rectal application is directly absorbed in the venous plexus of the rectum to be distributed thoughout the body by the blood circulation without passing the portal vein and the liver. Therefore, a rectally applicable medicament form is preferable particularly for the medicines of which the effective ingredient causes a disorder in the stomach when orally administrated or the ingredient is susceptible to decomposition in the digestive tract or in the liver resulting in decreased effectiveness of the medicine.
As is well known, the medicament forms for rectal application in general include suppositories and so-called rectal capsules.
Suppositories as a medicament form are prepared usually by dispersing the therapeutically active ingredient in a base such as cacao butter, polyethyleneglycol, mixture of higher fatty acid glycerides and the like solidifying and shaping the blend into a desired form, e.g. a conical or cannonball-like form, suitable for insertion into the coelom through the anus. Suppositories are the most widely used medicament form for rectal application and effective by releasing the effective ingredient in the rectum when melted at the body temperature or dissolved in the rectal fluid.
Suppositories present a very convenient means for rectal application of the medicine but not without various problems in the preparation and storage thereof. Several of the problems are that an efficient means is required for the uniform dispersion of the effective ingredient in the highly consistent suppository base, that suppositories are not a suitable medicament form for an ingredient susceptible to thermal decomposition because the ingredient must be distributed in the base molten by heating, that suppositories must be stored in a cool place because deformation of suppositories is unavoidable at a relatively high temperature and that specific facilities are necessary for the preparation thereof to be in compliance with the aforementioned problems.
On the other hand, a rectal capsule is a modification of the suppository in a sense and can be prepared in a manner similar to the preparation of soft capsules. That is, the therapeutically effective ingredient, alone or with admixture of other additives according to need, is shaped by lightly compressing and encapsulated and further shaped with a capsule base such as gelatin. Therefore, preparation of rectal capsules also requires specific facilities and skillful works.
In view of the above problems in the rectal capsules, it is another possible way to utilize an ordinary gelatin-made capsule for oral administration as the medicament form for rectal application. Several difficulties are, however, encountered in the use of gelatin capsules for rectal application. For example, medicines with acidity or in a liquid form cannot be encapsulated in both hard and soft gelatin-made capsules. Further, powdery medicines encapsulated in soft capsule are not free from the problem in the stability in addition to the burdensomeness in the preparation of the medicament form.
In view of the above problems in the medicament forms suitable for rectal application, the inventors have come to the idea of utilizing hard capsules shaped of an enterosoluble material for the medicament form for rectal application. Their investigations along this line have led to the discovery of an excellent enterosoluble material suitable for rectal application in the form of a hard capsule. An enteric material has been proposed which is a cellulose ether derivative which is a mixed ester of an alkylcellulose, hydroxyalkylcellulose or hydroxyalkyl alkylcellulose esterified with acidic succinyl groups and aliphatic monoacyl groups, e.g. acetyl groups. These materials are disclosed in U.S. patent application Ser. No. 140,478, filed Apr. 15, 1980 and thus it is known how to make such materials. The hard capsules shaped of the above mentioned cellulose derivative have excellent enteric solubility, intoxicity to the human body and stability with the elapse of time. Further, the capsules have sufficient pliability even without formulating a plasticizer and their disintegrability and smoothness on the surface permit their application as a medicament capsule for rectal application. In addition, the capsules shaped of the above mentioned cellulose derivative can be filled with any aqueous medicine in the form of an aqueous solution, aqueous suspension or emulsion so that a great advantage is obtained in the versatility of the medicines filling the capsule in comparison with other medicament forms.
In extending the investigations with the medicament capsules for rectal application formed of the hard capsule shells of the cellulose derivative, a very serious problem was encountered that the disintegrability of the capsules and the releasability of the effective ingredient contained in the capsule in the rectum are widely diversified among the individuals administrated with the medicament capsules by rectal application so that an extremely large difference was found in the concentration of the effective ingredient in the blood.